The pathogenesis of dental disease of the soft tissue is poorly understood. Gingivitis, the clinical manifestation which follows the accumulation of bacterial plaque in the gingival crevice area, usually progresses to periodontal disease. It is reasonable to suppose that dental plaque contains a primary factor or factors contributing to initiation of periodontal disease.
A wide variety of microorganisms present in the debris from the human gingival crevice have been identified qualitatively and quantitatively, but only recently have investigations focused on the immune response of the host to plaque material. Considerable evidence has accumulated that plaque microorganisms and/or their products initiate periodontal inflamation by altering the immune response of the host.
It is generally thought that oral bacteria sensitize the host, i.e., can stimulate the proliferation of lymphocytes and that the products of sensitization result in destruction of bone and soft tissues of the peridontium. Accordingly, it is highly unexpected that bacterial products would inhibit an immune response.
The immune response in humans and most animals in either humoral, i.e., mediated by antibodies, or cellular, i.e., mediated by sensitized lymphocytes. In either case, the immune response and accompanying inflammation may have both protective and destructive effects on the host tissue. The humoral reaction in man and other animals is provided by antibodies, immunoglobulin materials produced by lymphocytes, which circulate in the blood and are capable of chemically combining with "foreign matter" to neutralize it. However, in certain cases, the presence of a specific antibody may be undesirable. For example, antibodies directed toward antigens on the surface of a transplanted, foreign organ will result in destruction of the organ by the host.
The precise role of antibody-mediated immunity in the pathogenesis of periodontal disease is obscure, but serum antibodies against oral bacteria have been detected in patients with periodontal disease and the importance of cell-mediated immunity in periodontal disease has been suggested. The presence of bacterial factors capable of transforming lymphocytes and, presumably, enhancing antibody production, have been reported and these bacterial factors have been demonstrated in sonicates, extracts, and heated culture fluids from oral bacteria as well as sonicates or extracts of dental plaque and saliva. See generally, T. B. Higerd, et al "inhibitory Effects of Extracellular Products from Oral Bacteria on Human Fibroblasts and Stimulated Lymphocytes", Infection and Immunity, August, 1978, pp. 567-574, and the references cited therein, which are herein incorporated by reference.
Extracellular products of oral bacteria may be involved in the pathogenesis of periodontal disease, since the lesion is found distant from the dental plaque. These products might also interfere with the function of fibroblasts, since early loss of collagen in periodontal disease may be directly related to the ability of fibroblasts to produce or catabolize collagen. It has been found that extracellular products from cultured oral bacteria, in accordance with the instant invention, are capable of inhibiting both proliferation of human fibroblastoid cell lines and blast transformation of stimulated human peripheral lymphocytes from normal individuals. Therefore, such products may be implicated in the pathology of periodontal disease and/or may interfere with the immune defense of the host against invading microorganisms.
Immunosuppressive materials have been obtained from blood extracts, e.g., immunoglobin derived from human blood lymphocytes by Thomas et al (U.S. Pat. No. 4,009,257) and gamma-globulins isolated by Bonneau et al (U.S. Pat. No. 4,056,614). .gamma.-Linoleic acid is reported by Williams (U.S. Pat. No. 3,993,775) to have an immunosuppressive effect. Histaminase, an enzyme, in combination with an anti-microbial material, is said to substantially reduce reactions of the reticuloendothelial system (Van Leeuwen, U.S. Pat. No. 3,721,733).
It will be appreciated that, because suppression of a normal immune response may be highly desirable in certain clinical contexts, there is a need for additional sources and kinds of effective, non-toxic immunosuppressant materials.